Hormone replacement therapy has been known for some time. One particular aspect of hormone replacement therapy, known generally as estrogen replacement, has been used for over 30 years for women during or following menopause. The reason for estrogen replacement, which is usually accomplished through transdermal absorption or orally, is to make up for the decline in, or the low level of, estrogen produced by the body. Typically, estrogen production decreases and then declines dramatically during and after menopause. It is during this time period that estrogen replacement is normally prescribed by a physician. However, estrogen replacement can be prescribed in other circumstances where other causes account for a decline in estrogen production or if estrogen is produced at a lower than desirable level. This could occur in women not yet in menopause.
The reasons for estrogen replacement, which have been substantiated by scientific research over a number of years, include the prevention and/or treatment of osteoporosis and cardiovascular disease, as well as preventing age-related decline in mental function. Estrogen replacement has also been used to decrease age-related changes in appearance.
The most commonly prescribed estrogen for estrogen replacement is actually concentrated from horse urine, referred to generally as equine-conjugated estrogen or just equine estrogen. In addition, a single naturally occurring human estrogen metabolite, typically 17-beta estradiol, in the form of a “patch”, has also been and is currently prescribed. Many physicians and others have objected to equine estrogen as being inappropriate for human use and even possibly dangerous because of the fact that many individual horse estrogens are not present in human bodies and, hence, there is a lack of correlation between equine estrogen and the human estrogen which is to be replaced. There is also some evidence of the carcinogenic effect of equine estrogen.
As indicated above, the use of natural 17-beta estradiol (a single estrogen) typically occurs in the form of an estrogen patch. While clearly more appropriate for estrogen replacement than equine estrogen, this single estrogen is believed to be incomplete for estrogen therapy, because of the large number of different estrogens and their metabolites which normally circulate in the blood stream of human bodies, particularly in women.
In this regard, several specific human estrogens, sometimes referred to as “classical” human estrogens, have been the subject of extensive research in replacement therapy. These classical estrogens include estrone, estradiol (17-beta estradiol) and estriol. Estriol has been found to be relatively weak in its therapeutic benefits, while 17-beta estradiol is considered the most potent, but is generally agreed to be slightly carcinogenic. Estrone also has a carcinogenic effect, although both estrone and 17-beta estradiol are less carcinogenic than equine estrogens. There is disagreement with respect to the carcinogenic effect of estriol, ranging from non-carcinogenic or even anti-carcinogenic to slightly carcinogenic.
In an attempt to duplicate or mimic the presence of natural estrogens in the human body by replacement therapy, some physicians in the 1980s began to prescribe combinations of the three classical human estrogens, namely, a combination of estrone, 17-beta estradiol and estriol. Typically, the combination has been 80% estriol, 10% estrone and 10% estradiol, although these percentages have varied somewhat from formulation to formulation.
However, even with natural estrogen replacement, there is still concern relative to its carcinogenic effect as well as other undesirable possibilities. Given the fact that estrogen replacement has been documented to have considerable health benefits, it is certainly desirable to develop an estrogen replacement formulation which is not only appropriate, natural and effective, but also is designed to prevent or minimize negative side effects, including carcinogenic side effects.